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Decreased fertility is also observed in HD animal models and HD male patients, due to altered spermatogenesis and sperm function, thus resulting in reduced fertilization potential. Although some pharmaceuticals are currently utilized to mitigate HD symptoms, an effective treatment that remedies the pathogenesis of the disease is yet to be approved by the FDA. Identification of genes and relevant diagnostic biomarkers and therapeutic target pathways including glycolysis and mitochondrial complex-I-dependent respiration may be advantageous for early diagnosis, management, and treatment of the disease. This review addresses the HD pathway in neuronal and sperm metabolism, including relevant gene and protein expression in both neurons and spermatozoa, indicated in the pathogenesis of HD. Furthermore, zinc-containing and zinc-interacting proteins regulate and\/or are regulated by zinc ion homeostasis in both neurons and spermatozoa. Therefore, this review also aims to explore the comparative role of zinc in both neuronal and sperm function. Ongoing studies aim to characterize the products of genes implicated in HD pathogenesis that are expressed in both neurons and spermatozoa to facilitate studies of future treatment avenues in HD and HD-related male infertility. The emerging link between zinc homeostasis and the HD pathway could lead to new treatments and diagnostic methods linking genetic sperm defects with somatic comorbidities.<\/jats:p>","DOI":"10.3390\/ijms23137163","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"7163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spermatozoan Metabolism as a Non-Traditional Model for the Study of Huntington\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Meghan","family":"Lawlor","sequence":"first","affiliation":[{"name":"Division of Animal Science, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2964-5940","authenticated-orcid":false,"given":"Michal","family":"Zigo","sequence":"additional","affiliation":[{"name":"Division of Animal Science, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-0131","authenticated-orcid":false,"given":"Karl","family":"Kerns","sequence":"additional","affiliation":[{"name":"Division of Animal Science, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Animal Science, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-9128","authenticated-orcid":false,"given":"In Ki","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA"},{"name":"Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Easley IV","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA"},{"name":"Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-2823","authenticated-orcid":false,"given":"Peter","family":"Sutovsky","sequence":"additional","affiliation":[{"name":"Division of Animal Science, University of Missouri, Columbia, MO 65211, USA"},{"name":"Department of Obstetrics, Gynecology and Women\u2019s Health, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kim, A., Lalonde, K., Truesdell, A., Gomes Welter, P., Brocardo, P.S., Rosenstock, T.R., and Gil-Mohapel, J. 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